Final Diagnosis -- Hemolytic transfusion reactions caused by the Kidd blood group




Transfusion Reactions

These two cases represent hemolytic transfusion reactions caused by the Kidd blood group. Case one is a delayed hemolytic transfusion reaction (DHTR) and case two is an acute hemolytic transfusion reaction (AHTR). What should I do if a patient developed transfusion reaction?

  2. Keep the IV open with 0.9% NaCL.
  3. Check the product tags & patient identification.
  4. Notify the Blood Bank.

    If the transfusion is terminated:

  5. Collect & send blood & urine samples to the Blood Bank.
  6. Send the unit, tags & the blood administration set to the Blood Bank [1].

A transfusion reaction workup is initiated by the clinician. Laboratory findings in AHTRs include hemoglobinemia, hemoglobinuria, elevated lactate dehydrogenase (LDH), hyperbilirubinemia, and low haptoglobin [3]. During hemolysis, hemoglobin decreases as red cells are been destroyed. Haptoglobin is a mucoprotein that binds to free hemoglobin in the plasma, and thus decreases in hemolysis. If the amount of free hemoglobin is too much for the kidney to tolerate the patient can develop hemoglobinuria. The blood urea nitrogen and creatinine can be elevated if renal dysfunction occurs. The direct antiglobulin test (DAT) may be positive [3].

A transfusion reaction workup in the blood bank includes clerical check, visual inspection for hemolysis (serum), and DAT. The DAT detects the presence of antibody attached to red cells in the patient's circulation. DAT can be positive if there are alloantibodies attached to the transfused red cells, or there are antoantibody bound to patient's own RBCs (if the patient has not been transfused) [2]. DAT starts with the patient's red cells, which are washed to remove unbound antibodies, then polyspecific anti-globulin reagent is added to observe agglutination. If the polyspecific DAT is positive, then anti- IgG, or anti-C3d specific reagent is used. If the DAT is positive with anti-IgG, an elution procedure is performed. An elution procedure is when an antibody is removed from the red cells with acidic glycine solution and the solution is called an eluate. A red cell panel is performed to identify the antibody in the eluate [2]. Newly developed antibodies may be initially only detected in the eluate and not the serum, because the eluate concentrates the antibody [1]. Cases of positive DAT tests with anti-IgG and negative eluates may be due to the eluate was not tested against panel cells with the antigen (in the case of low incidence antigens) or nonspecific IgG binding [1].

Hemolytic Transfusion Reactions

DHTR is an anamnestic antibody production (preformed antibodies are absent or too low for methods to detect). The patient has been exposed to the antigen previously and lymphocytes are ready to produce antibodies when exposed. This usually occurs 5 to 14 days after transfusion with more commonly extravascular hemolysis but some cases have intravascular hemolysis [2 and 3]. Signs include jaundice, fever, pain or shortness of breath. Laboratory findings in DHTRs may include anemia, elevated LDH, hyperbilirubinemia, low haptoglobin, the present a new red cell antibody or antibodies, and a positive DAT [3]. Kidd alloantibodies account for 1/3 of DHTRs. The remainder of DHTRs are caused by anti- D, c, E, K or Fya [2]. Subsequent units given to the patient must be antigen negative for the antibody that caused the reaction. Most delayed hemolytic reactions are not clinically significant and not reported [1].

Acute hemolytic transfusion reaction is the activation of complement, release of cytokines inducing a systemic inflammatory response within 24 hours of transfusion [3]. There are two explanations for the Kidd blood group's activation of complement. Kidd antigens are thought to be clustered close together allowing for complement activation by IgG and since a subset of Kidd are IgM, Kidd IgM antibodies activate complement [4 and 5]. Signs include fever, tachycardia, hypotension, pain, or shortness of breath [3]. In AHTRs, there may be renal damage due to vasoconstriction. Free hemoglobin released into the bloodstream following intravascular hemolysis binds to nitric oxide causing vasoconstriction and nephrotoxicity. C8-9 mediated destruction is in involved in AHTRs [6]. Most AHTRs are from intravascular hemolysis and the most common cause is from ABO incompatibility [3].

Management of hemolysis includes recognition and stop the transfusion. For further units, administer antigen negative units. Supportive measures for hypotension are pressors and fluid resuscitation. Furosemide and fluids can be given to protect renal function. The patient's renal function should be monitored [6]. In severe cases, exchange transfusion with antigen negative units can be considered [3].

Kidd Blood Group System

Jka was discovered in 1951 when an undiscovered antibody caused hemolytic disease of the newborn in the sixth child of Mrs. Kidd. JK was the initials of the baby. Jkb was found two years later in a woman with a transfusion reaction [7]. The Kidd blood group has two co-dominant antigens, Jka and Jkb, on SLC14A1, an urea transporter protein. The red cell urea transporter, HUT11 (human urea transporter 11) contains the Kidd antigens. The transporter uptakes urea in the renal medulla and disperses it away from the kidney without affecting the cell size. The Jka-b- is not associated with a clinical significant disorder from lacking the urea transporter [1].

Anti - Jka and Jkb are mostly IgG1 and IgG3 with minor component of IgG2, IgG4, or IgM [1]. Antibodies can cause both intravascular and extravascular hemolysis [8]. Antibodies rapidly decease in the absence of the antigen and may be undetectable on antibody screening [1]. Both Anti- Jka and Anti-Jkb can cause AHTRs and DHTRs. To enhance Kidd antibody identification, use a fresh sample, use proteolytic enzymes to destroy other antigens on the red blood cell and make the Kidd antigen more available for binding and use LISS to promote IgG binding [9].

Kidd antibodies can cause hemolytic disease of the fetus/ newborn but is usually not severe [7]. Anti- Jka is more frequent and more severe [8]. Kidd antibodies are characteristically found with other antibodies [7]. Auto antibodies against Kidd antigens have been seen in autoimmune hemolytic anemia including drug induced hemolysis. Other sources of auto antibodies to Kidd antigens have been documented from food preservatives, cosmetics and Proteus mirabilis [9].

Table 5: Kidd Phenotype Frequencies

(Harmening, Modern Blood Banking and Transfusion Practices, 4th edition, 1999 [9] ) Jka is more prevalent than Jkb in African Americans. Most of our blood product donations in Pittsburgh are from Caucasians. Since 72% of Caucasians have Jkb antigens and 57% of African Americans are Jkb-, there is the potential to make anti-Jkb antibodies with exposure to blood products in this area.

Kidd Protein

The Kidd gene is located on chromosome 18 and contains 11 exons however only exons 4- 11 code for the protein [1]. The Kidd glycoprotein protein has ten transmembrane domains and the N and C termini are located intracellularly. The Kidd polymorphism is located on the fourth loop and caused by a single amino acid substitution. Kidd protein is expressed on red cell surfaces, neutrophils and endothelial cells in the kidney [7 and 8]. The phenotype is the product of alleles in which Jka is Asp280 and Jkb is Asn280 [1].

Kidd Blood Group in the Literature

Kidd antibodies may function as histocompatibility antigens in renal transplants and may be linked to acute transplant rejections [10].


  1. Roback, J. D., & American Association of Blood Banks. Technical Manual. 16th ed. Bethesda, Md.: Aabb; 2008.
  2. Petrides, M., Stack, G., Cooling, L., & Maes, L. Y.. Practical Guide to Transfusion Medicine. 2nd ed. Amer Assn of Blood Banks; 2007.
  3. Mintz, Paul D,ed. Transfusion Therapy: Clinical Principles and Practices. 3rd edition. Bethesda, MD: AABB Press; 2011.
  4. McCullough, J. J.. Transfusion Medicine. New York: McGraw-Hill; 1998.
  5. Yates, J., Howell, P., Overfield, J., Voak, D., Downie, D. M., & Austin, E. B. IgG anti-Jka/Jkb antibodies are unlikely to fix complement. Transfusion Medicine. 1998; 2: 133-140.
  6. Klein, H. G., Mollison, P. L., Anstee, D. J., & Mollison, P. L. Mollison's Blood Transfusion in Clinical Medicine. 11th ed. Malden, Mass.; Oxford: Blackwell Pub.; 2005.
  7. Westhoff, C. M., & Reid, M. E. Review: The kell, duffy, and kidd blood group systems. Immunohematology / American Red Cross. 2004; 20(1):37-49.
  8. Rossi, E. C., & Simon, T. L. Rossi's Principles of Transfusion Medicine. 4th ed. Hoboken, NJ: Wiley-Blackwell; 2009.
  9. Harmening, D. Modern Blood Banking and Transfusion Practices. 4th ed. Philadelphia: F.A. Davis; 1999.
  10. Holt, S., Donaldson, H., Hazlehurst, G., et al. Acute transplant rejection induced by blood transfusion reaction to the kidd blood group system. Nephrology Dialysis Transplantation. 2004; 19(9):2403-2406.

Contributed by Lisa Radkay, MD and Lirong Qu, MD, PhD

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